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Natural killer cell deficiency

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Related Terms
  • Amniocentesis, antibiotics, antifungals, antimicrobials, antivirals, autosomal recessive disorder, bacterial infection, cancer, chorionic villus sampling, cytokines, genetic disorder, immune, immune defense system, immune reaction, immune response, immune system, infection, inherited disorder, interferons, natural killer cell, malignant tumor, natural killer cell function assay, NK cell, NK cell function assay, prenatal DNA analysis, prenatal testing, recurrent infections, tumor, viral infection, white blood cells.

Background
  • Natural killer (NK) cell deficiency is an inherited immune system disorder in which the patient has low or absent levels of a certain type of white blood cells called NK cells. The NK cells help the immune system fight against disease and infection. These cells recognize and destroy body cells that have become infected with viruses or cancer. They have pouches, called granules, which are filled with chemicals that destroy infected cells on contact.
  • Healthy individuals normally experience fluctuations in the number of NK cells in the blood. These cells rapidly increase in response to an infection and then decrease for five to seven days after the infection.
  • Patients with NK cell deficiency are born with low or nonexistent levels of NK cells. As a result, these patients are vulnerable to infections. Life expectancy varies among patients, depending on how severe the deficiency. The condition may lead to fatal infections and recent studies have suggested patients may have an increased of developing cancer.
  • The exact incidence of NK cell deficiency remains unknown.
  • Currently, there is no specific treatment for NK cell deficiency. Instead, treatment focuses on curing infections associated with the disorder. Treatment of infections is generally longer in patients with NK cell deficiency than in the general population because they respond more slowly.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. American Cancer Society. . Accessed May 24, 2007.
  2. Khan S, Myers K. Persistence of Natural Killer (NK) cell lymphocytosis with hyposplenism without development of leukaemia. BMC Clin Pathol. 2005 Sep 7;5:8. .
  3. Molling JW, Langius JA, Langendijk JA, et al. Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol. 2007 Mar 1;25(7):862-8. .
  4. National Cancer Institute. . Accessed May 24, 2007.
  5. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2007. Accessed May 24, 2007.
  6. Orange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):399-409. .
  7. Whiteside TL, Herberman RB. Role of human natural killer cells in health and disease. Clin Diagn Lab Immunol. 1994 Mar;1(2):125-33. .

Causes
  • Natural killer (NK) cell deficiency is a genetic disorder that is passed down from parents to their children. Currently, five different genes have been shown to cause NK cell deficiency. Each of these genes is passed down as an autosomal recessive trait. In other words, the patient must inherit one mutated gene from each parent in order to develop the disorder. Individuals who only have one mutated gene and do not experience symptoms are called carriers.
  • Carriers have a 50% chance of passing the abnormal gene to each of their children. If both parents are carriers of the gene, there is a 25% chance that each of their children will inherit the disease and a 50% chance that each of their children will be a carrier.

Symptoms
  • Patients with natural killer (NK) cell deficiency suffer from frequent infections, especially lung infections and herpes virus infections.
  • There is also evidence suggesting that patients with NK cell deficiency have an increased risk of developing cancer. This is because NK cells are the body's first line of defense against cancerous growths in the body. Some studies also suggest that cancer patients with NK cell deficiency may not respond as well to treatments as patients who do not have the disorder.

Diagnosis
  • DNA analysis: A DNA analysis is the most conclusive diagnostic test for natural killer (NK) cell deficiency. During the procedure, a small sample of the patient's blood is sent to a laboratory that performs genetic testing. The sample is then analyzed for the presence of genes that are associated with the disorder. This test may be performed if NK cell deficiency is suspected or if it is suspected that the patient may be a carrier.
  • Natural killer cell count: If NK cell deficiency is suspected, a natural killer cell count may be conducted. During the procedure, a small sample of blood is taken from the patient, and the number of NK cells is measured. In healthy individuals, NK cells make up about 15% of the mononuclear cells (cells with one nucleus) in the blood. These levels typically fluctuate to some degree. For instance, patients experience a rapid increase in NK cells in response to an infection, followed by a decrease for five to seven days after the infection. Patients who have low or absent levels of NK cells and are not recovering from a recent infection receive a positive diagnosis.
  • Natural killer cell function assay: An NK cell function assay can determine whether a patient has deficient levels of NK cells in the blood. A sample of blood is taken from the patient. A special machine removes the NK cells from the sample. These cells are then placed on a petri dish along with cells (such as viruses) that should trigger them to kill. If the patient has normal levels of healthy NK cells, the NK cells will kill the other cells on the petri dish. After a few hours, a colored dye is added to the petri dish. This dye will only saturate the dead cells. Then, a device called a flow cytometer will then measure how many cells the NK cells killed. If the NK cells do not kill enough of the cells, a positive diagnosis can be made.
  • Prenatal DNA analysis: Pregnant mothers may have their unborn children tested for NK cell deficiency. In order to retrieve a sample of the fetus' cells for testing, amniocentesis or chorionic villus sampling may be performed. During amniocentesis, a long, thin needle is inserted into the pregnant woman's abdominal wall and into the uterus. A small amount of fluid is removed from the sac surrounding the fetus. During chorionic villus sampling (CVS), a small piece of tissue, called chorionic villi, is removed from the placenta. There are risks associated with these both of these procedures, including miscarriage. Patients should discuss the potential risks and benefits of these procedures with their healthcare providers.

Treatment
  • General: There is no specific treatment for natural killer (NK) cell deficiency. Instead, treatment focuses on curing infections associated with the disorder. Treatment of infections generally lasts longer for patients with NK cell deficiency than for patients who do not have the disorder. This is because NK patients have weakened immune systems that are slower to respond to treatments.
  • Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs, or supplements because they may interact with treatment. Also, patients should take medications exactly as prescribed by their doctors. If treatment is stopped too quickly, the infection may recur.
  • Antimicrobials: Antibiotics are used to treat bacterial infections, antifungals are used to treat fungal infection, and antivirals are used to treat viral infections. The type of medication, dose, and length of treatment depends on the type and severity of the infection, as well as the patient's overall health.
  • Interferons: Interferons, which are agents that stimulate the production of NK cells, have been used to treat NK cell deficiency. They are typically used when the patient develops severe infections. Interferons are either man-made or derived from human blood donations. They contain cytokines, which are chemical messengers in the body that stimulate the production of NK cells. This treatment is injected into the patient to help increase the number of NK cells during an infection.

Integrative therapies
  • Good scientific evidence:
  • Ginseng: For more than 2,000 years, the roots of this slow-growing plant have been valued in Chinese medicine. Several studies suggest that ginseng can effectively enhance immune system function.
  • Avoid ginseng with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in the ginseng formulation.
  • Zinc: Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc appears to be an essential trace element for the immune system, but there is little research on the effect of zinc supplementation on immune function and most studies focus on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a firm conclusion can be made.
  • Zinc is generally considered safe when taken at recommended doss. Avoid zinc chloride, since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used because studies cannot rule out the possibility of harm to the fetus.
  • Unclear or conflicting scientific evidence:
  • Arginine (L-arginine): L-arginine helps maintain the body's fluid balance, fights infection, and aids in wound healing, hair growth, sperm production, and blood vessel relaxation. Preliminary research results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.
  • Avoid if allergic to arginine. Avoid with history of stroke, liver disease, or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (like warfarin), blood pressure drugs, or herbs or supplements with similar effects. Check blood potassium levels.
  • Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. There are published reports from China of white blood cell counts increasing during the use of astragalus preparations, although details are limited. High-quality human research is necessary before a firm conclusion can be drawn.
  • Avoid if allergic to astragalus, peas, any related plants, or with a history of Quillaja bark-induced asthma. Avoid with aspirin, aspirin products, or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant, or autoimmune diseases (such as HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
  • Beta-carotene: Beta-carotene is a member of the carotenoids. They are naturally found in many fruits, grains, oil, and vegetables (such as green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers). Preliminary research of beta-carotene for immune system maintenance or stimulation shows mixed results. Further research is needed before a conclusion can be drawn.
  • Avoid if sensitive to beta-carotene, vitamin A, or any other ingredients in beta-carotene products.
  • Cat's claw: Cat's claw is widely used in the United States and Europe, and it is one of the top herbal remedies sold, despite a lack of high-quality human evidence. In Germany and Austria, cat's claw is only available by prescription. A few early studies suggest that cat's claw may boost the immune system. However, results from different studies have not agreed with each other. Further research is needed before a firm conclusion can be made.
  • Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family, such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding. Cat's claw may be contaminated with other Uncaria species. Reports exist of the potentially toxic Texan grown plant Acacia gregii being substituted for cat's claw.
  • Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, and fruits, as well as shellfish, avocado, beef, and animal organs, such as the liver and kidney. Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have side effects on the immune function, although the exact mechanism is unclear.
  • Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down's syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism, such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6 milligrams/liter. Use cautiously with anemia, arthralgia, and myalgia. Use cautiously if taking oral contraceptives (birth control pills). Use cautiously if at risk for selenium deficiency. The recommended dietary allowance (RDA) is 1,000 micrograms for pregnant women. The RDA is 1,300 micrograms for breastfeeding women.
  • Echinacea: The roots and herb of Echinacea species have attracted recent scientific interest because they may have immune stimulant properties. Echinacea has been studied alone and in combination with other herbs or supplements for immune system stimulation (including in patients receiving cancer chemotherapy). It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.
  • Avoid if allergic to plants in the Asteraceaeor Compositaefamily (ragweed, chrysanthemums, marigolds, daisies). Avoid Echinacea injections. Avoid if history of liver disease or if taking amoxicillin. Avoid in transplant patients. Use cautiously if driving or operating heavy machinery or if history of asthma, diabetes, conditions affecting the immune systems (like lupus, TB, AIDS-HIV), and rheumatologic conditions (rheumatoid arthritis). Avoid if pregnant or breastfeeding. Tinctures may contain large amounts of alcohol.
  • Gamma linolenic acid (GLA): Gamma linolenic acid (GLA) is a dietary fatty acid. It is found in many plant oil extracts. A limited amount of GLA is found naturally in human breast milk, cold-water fish, and organ meats (such as liver). GLA is commonly sold as a dietary supplement either in the form of capsules or oil. Few clinical trials have investigated the effects of GLA on immune responses in healthy human subjects. Results from one randomized, clinical trial suggest that GLA, as blackcurrant seed oil, may offer some benefits. Further, well-designed clinical trials are required before definite conclusions can be made.
  • Use cautiously with drugs that increase the risk of bleeding, such as anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.
  • Goldenseal: Goldenseal is one of the five top-selling herbal products in the United States. However, there is little scientific evidence about its safety or effectiveness. Goldenseal can be found in dietary supplements, eardrops, feminine cleansing products, cold/flu remedies, allergy remedies, laxatives, and digestive aids. Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little human or laboratory evidence in this area. More research is needed before a firm conclusion can be drawn.
  • Avoid if allergic or hypersensitive to goldenseal or any of its constituents, like berberine and hydrastine. Use cautiously with bleeding disorders, diabetes, or low blood sugar. Avoid if pregnant or breastfeeding.
  • Maitake mushroom: Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Maitake has been used both as a food and for medical conditions. Animal and laboratory studies suggest that beta-glucan extracts from maitake may alter the immune system. However, no reliable studies in humans are available.
  • Maitake has not been studied thoroughly in humans, and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to Grifola frondosa (maitake). Use cautiously with a history of low blood pressure, diabetes, or with drugs, herbs, or supplements that treat such conditions. Avoid if pregnant or breastfeeding.
  • Massage: Various forms of massage have been practiced to promote well-being, relaxation, pain-reduction, stress-relief, musculoskeletal injury healing, sleep enhancement, and quality of life. Preliminary evidence suggests massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.
  • Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously if history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.
  • Meditation: A common goal of meditation is to attain a state of thoughtless awareness of sensations and mental activities occurring at the present moment. Preliminary research reports increased antibody response after meditation. Further study is needed to confirm these findings.
  • Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies and should not be used as the sole approach to illnesses.
  • Mistletoe: Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints. A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further research is needed to confirm these results.
  • Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening, shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or with cholinergics.
  • Probiotics: Probiotics are beneficial bacteria and are sometimes called "friendly germs." They help maintain a healthy intestine and aid in digestion. They also help keep harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. Lactobacillus in fermented milk, low-fat milk, or lactose-hydrolyzed low-fat milk may enhance immune function. Bifidobacterium may as well, including in the elderly. However, commercially produced yogurt may not yield similar benefits. There is some evidence that probiotics added during food preparation (e.g. waffles with Enterococcus faecium M-74 added) can enhance immune functioning. More studies are needed, particularly with yogurt, before a firm conclusion can be made.
  • Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
  • Vitamin A (retinol): Vitamin A is a fat-soluble vitamin that is derived from two sources: retinoids and carotenoids. Retinoids are found in animal products (such as liver, kidney, eggs, and dairy products). Carotenoids are found in plants, such as dark or yellow vegetables and carrots. Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.
  • Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.
  • Vitamin B6 (pyridoxine): Major sources of vitamin B6 include cereal grains, legumes (beans), vegetables (such as carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 is important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a recommendation can be made.
  • Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). The RDA for pregnant women is 1.9 milligrams per day. There is some concern that high-dose pyridoxine taken by a pregnant mother can cause seizures in a newborn. The RDA in breastfeeding women is 2 milligrams per day.
  • Vitamin E: Vitamin E exists in eight different forms: alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.
  • Avoid if allergic or hypersensitive to vitamin E. For short periods of time, vitamin E supplementation is generally considered safe at doses up to 1,000 milligrams per day. Avoid doses higher than 1,000 milligrams a day. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders. The recommended dose of vitamin E for pregnant women of any age is 15 milligrams, and the recommended dose for breastfeeding women of any age is 19 milligrams. Use beyond this level in pregnant women is not recommended.
  • Fair negative scientific evidence:
  • DHEA (dehydroepiandrosterone): DHEA (dehydroepiandrosterone) is a naturally occurring hormone that is produced by the adrenal glands. Some authors of textbooks and review articles have suggested that DHEA can stimulate the immune system. However, current scientific evidence does not support this claim.
  • Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizure ,or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
  • Lycopene: Lycopene is a carotenoid found in tomatoes; it is present in human serum, liver, adrenal glands, lungs, prostate, colon, and skin. It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans report no effects on the immune system.
  • Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

Prevention
  • Currently, there is no known method of prevention of natural killer (NK) cell deficiency..
  • Patients who have the disorder may wish to receive genetic counseling. A counselor will provide information and answer questions about the risk of passing the disorder on to the patient's children
  • Patients can take precautions to avoid contracting infections associated with the disease. Patients should thoroughly wash their hands with soap and water. Patients should talk to their healthcare providers about recommended immunizations. Patients should avoid close contact with individuals who have contagious illnesses because they have an increased risk of contracting infections.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.


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